Incidence Of Pneumonitis Research Articles

Efficacy and safety of immune checkpoint inhibition combined with concurrent chemoradiotherapy in patients with stage III unresectable non-small cell lung cancer: A systematic review and meta-analysis.

In patients with unresectable, stage III non-small cell lung cancer (NSCLC), durvalumab maintenance after concurrent chemoradiotherapy (cCRT) was shown to improve survival over placebo. As subgroup analyses indicated better outcomes with earlier start of durvalumab, several trials evaluated concomitant checkpoint inhibition (CPI) with cCRT. However, this may introduce an increased risk of treatment-related pulmonary toxicity. We conducted a systematic review and meta-analysis of clinical trials of combined cCRT plus CPI followed by CPI maintenance in patients with stage III NSCLC. Endpoints included incidence of pneumonitis by any cause, objective response rate (ORR), progression-free (PFS), and overall survival (OS). A total of 7 trials comprising 653 patients were included. In trials of single-agent CPI with cCRT, pneumonitis occurred in 33 % of patients (95 % confidence interval [CI], 28-39) with 7 % (5-9) having CTCAE grade 3-5. In one trial, double CPI (PD-1 and CTLA4) plus cCRT was associated with excessive pneumonitis-related mortality of 16 % (4-40). Across all trials, ORR was 69 % (63-76). Median PFS and OS were 16.3 (95 % CI, 14.0-20.5) and 39.5 months (35.3-45.9), respectively. Three-year PFS and OS were 36.8 % (95 % CI, 32.7-41.4) and 53.1 % (49.1-57.4). Sensitivity analysis showed that induction chemoimmunotherapy prior cCRT plus CPI was associated with improved PFS of 48.0 % at 3 years (95 % CI, 40.7-56.7) in one trial. Addition of single-agent CPI to cCRT is manageable in selected patients with stage III NSCLC. Efficacy outcomes appear to be in line with previous data of cCRT followed by CPI maintenance.

Efficacy and safety of first-line nivolumab plus ipilimumab treatment in elderly patients (aged ≥ 75 years) with non-small cell lung cancer

PurposeNivolumab plus ipilimumab (Nivo-Ipi) combination therapy is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC). However, its effectiveness and feasibility in elderly patients (aged ≥ 75 years) remain unclear. This study aimed to investigate the efficacy and safety of first-line Nivo-Ipi therapy in elderly patients with NSCLC.MethodsThis retrospective study included 57 patients with NSCLC (52 men and 5 women), aged ≥ 75 years (range: 75–86) who received first-line Nivo-Ipi therapy from December 2020 to November 2022 at four institutes in Japan. Patient characteristics, therapeutic efficacy, and the incidence and severity of adverse events (AE) were assessed.ResultsThe overall response rate was 42.1%, the disease control rate was 73.6%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.1 months. Common Grade ≥ 3 AEs included pneumonitis, elevated aspartate transaminase, elevated alanine transaminase, adrenal insufficiency, and colitis. No treatment-related deaths were reported. PFS and OS were longer in patients who experienced treatment-related AEs. Patients with and without AEs had a median PFS of 11.7 and 2.8 months, respectively. Similarly, the median OS of patients with and without AEs was 20.4 and 9.0 months, respectively.ConclusionFirst-line Nivo-Ipi therapy is effective in elderly patients with NSCLC. Although there was an increased incidence of pneumonitis, the treatment was manageable and presented as a viable treatment option. Notably, the occurrence of treatment-related AEs was associated with improved clinical outcomes, suggesting a potential prognostic value of AEs in this population.

Radiotherapy combined with chemoimmunotherapy improves survival compared to chemoimmunotherapy alone as first-line treatment for oligometastatic esophageal squamous cell carcinoma.

To evaluate the safety and efficacy of radiotherapy combined with chemoimmunotherapy (RCIT) versus chemoimmunotherapy (CIT) alone as first-line treatment for oligometastatic esophageal squamous cell carcinoma (OESCC) at initial diagnosis. We retrospectively evaluated 140 patients newly diagnosed with OESCC who received RCIT or CIT as first-line treatment between June 2018 and December 2021. Among them, 76patients were in the RCIT cohort and 64patients in the CIT cohort. Propensity score matching (PSM) was used to simulate random allocation. After 1:1 PSM, 61well-paired patients were selected. The median follow-up duration was 34.7 months (95%CI: 30.6-38.8 months). After PSM, the median PFS for the RCIT and CIT groups was 10.9 (95%CI: 9.4-12.4) months and 7.3(95%CI: 6.0-8.7) months, respectively (P = 0.004). The median OS for the RCIT and CIT groups was 22.4 (95%CI: 17.5-27.4) months and 13.4 (95%CI: 10.9-15.9) months, respectively (P = 0.031). There were significant differences in PFS (median PFS: 12.9 vs.8.6 vs.7.3months, P = 0.003) between the group receiving radiotherapy (RT) for all lesions, the group receiving RT for partial lesions, and the CIT group, while OS was on the threshold of significance (median OS: 29.4 vs. 17.3 vs. 13.4 months, P = 0.052). No significant differences in the incidence of grade3 or higher (G3+) treatment-related adverse events (TRAEs) were observed between the two groups. However, the incidence of G3+ pneumonitis (13.1% vs 1.6%, P = 0.038) were higher in the RCIT group compared to the CIT group. RCIT as first-line treatment for OESCC was safe and efficacious. RCIT improved PFS/OS compared to CIT without increasing the overall high grade toxicity rate. However, the increased incidence of pneumonitis due to RT implementation cannot be disregarded.

CD73/adenosine dynamics in treatment-induced pneumonitis: balancing efficacy with risks of adverse events in combined radio-immunotherapies.

Consolidation with PD-1/PD-L1-based immune checkpoint blockade after concurrent platinum-based chemo-radiotherapy has become the new standard of care for advanced stage III unresectable non-small cell lung cancer (NSCLC) patients. In order to further improve therapy outcomes, innovative combinatorial treatment strategies aim to target additional immunosuppressive barriers in the tumor microenvironment such as the CD73/adenosine pathway. CD73 and adenosine are known as crucial endogenous regulators of lung homeostasis and inflammation, but also contribute to an immunosuppressive tumor microenvironment. Furthermore, the CD73/adenosine pathway can also limit the immune-activating effects of cytotoxic therapies by degrading the pro-inflammatory danger molecule ATP, which is released into the tumor microenvironment and normal lung tissue upon therapy-induced cell damage. Thus, while targeting CD73 may enhance the efficacy of radio-immunotherapies in cancer treatment by mitigating tumor immune escape and improving immune-mediated tumor killing, it also raises concerns about increased immune-related adverse events (irAEs) in the normal tissue. In fact, combined radio-immunotherapies bear an increased risk of irAEs in the lungs, and additional pharmacologic inhibition of CD73 may further enhance the risk of overwhelming or overlapping pulmonary toxicity and thereby limit therapy outcome. This review explores how therapeutic interventions targeting CD73/adenosine dynamics could enhance radiation-induced immune activation in combined radio-immunotherapies, whilst potentially driving irAEs in the lung. We specifically investigate the interactions between radiotherapy and the CD73/adenosine pathway in radiation pneumonitis. Additionally, we compare the incidence of (radiation) pneumonitis reported in relevant trials to determine if there is an increased risk of irAEs in the clinical setting. By understanding these dynamics, we aim to inform future strategies for optimizing radio-immunotherapy regimens, ensuring effective cancer control while preserving pulmonary integrity and patient quality of life.

Adaptive radiation strategy with V20 limitation associates with survival benefit and lower incidence of symptomatic radiation pneumonitis in stage III NSCLC patients receiving concurrent immunotherapy and thoracic radiation.

To evaluate the efficacy and the incidence of symptomatic radiation pneumonitis (RP) of the adaptive radiation strategy with V20 limitation in stage III non-small cell lung cancer (NSCLC) patients receiving concurrent immunotherapy and radiotherapy Materials and Methods: We retrospectively reviewed stage III NSCLC patients received thoracic radiation with or without immunotherapy from January 2015 to September 2024 in the Third Xiangya Hospital. The overall survival (OS), progression free survival (PFS), objective response rate (ORR), and the incidence of symptomatic RP were compared among patients stratified by the sequential of immunotherapy and radiotherapy. 45 patients received concurrent immunotherapy and radiotherapy with application of the adaptive radiation strategy (the CIR group). 32 patients received simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT), 26 patients received 2 to 4 cycles neoadjuvant immuno-chemotherapy before the concurrent immunotherapy and radiotherapy, 7 patients received thoracic radiotherapy with a prescribed dosage of 50 Gy, and 10 patients received radiotherapy with CTV omission. 86.67 % (39/45) patients had a V20 ≤ 20 %. The ORR was 86.67 %. The median PFS of these patients was significantly longer than those received concurrent chemo-radiotherapy followed by immunotherapy (the PACIFIC paradigm, HR, 2.40; 95 % CI, 1.15 to 5.02; log-rank p = 0.013; median, 28.6 vs. 16.1 months p = 0.013). The median OS was not reached. 13.3 % patients in the CIR group experienced grade ≥ 2 RP and the incidence was significantly lower than that of patients received radiotherapy without immunotherapy or concurrent chemo-radiotherapy with immunotherapy consolidation. The application of adaptive radiotherapy strategies with V20 limitation demonstrated robust antitumor activity and reduced pulmonary toxicity in stage III NSCLC patients receiving concurrent ICIs treatment and thoracic radiation. This treatment modality deserves further validation as a promising therapy in patients with treatment-naive, unresectable, stage III NSCLC.

Cancer type-specific adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis.

The distribution of adverse events (AEs) triggered by immune checkpoint inhibitors (ICIs) across different cancer types has never been demonstrated. Randomised controlled trials exclusively assessing ICI monotherapy in cohorts of over 100 patients were considered. Our primary outcome was a comprehensive summary of the distribution of all-grade treatment-related adverse events (TRAEs) as well as serious TRAEs (CTCAE grade 3 or higher) across different malignancies. The study is registered with PROSPERO CRD42023387934. 75 trials that enrolled over 100 patients were included. While investigating the incidence of each TRAE across various cancers, we found special linkages existed between certain TRAEs and particular cancer types. In anti-PD-1 monotherapy group, melanoma patients experienced the most frequent fatigue (31.1%, 95% CI 29.7%-32.5%); the incidences of severe pneumonitis and other respiratory disorders were highest in Hodgkin lymphoma (4.1%, 95% CI 1.5%-8.6%; 4.1%, 95% CI 1.5%-8.6%, respectively). Among individuals undergoing single-agent anti-PD-L1, higher frequency of all-grade pruritus occurred in 19.0% of renal cell carcinoma (RCC) patients (95% CI 15.2%-23.2%), and the highest probability of developing other severe musculoskeletal disorders was observed in patients with RCC (6.2%, 95% CI 4.0%-9.0%). In anti-CTLA-4 monotherapy, the incidences of both all-grade and severe diarrhea occurred most frequently in prostate cancer patients (41.9%, 95% CI 37.9%-47.9; 14.8%, 95% CI 11.5%-18.7%, respectively). This is the first comprehensive study addressing the distribution of various TRAEs across cancer types. Our research emphasizes the significance of considering cancer-specific TRAEs when using ICIs for treatment.

Real-world analysis of the incidence and risk factors of pneumonitis in non-small cell lung cancer patients treated with combined thoracic radiotherapy and immunotherapy

Abstract Objectives Combining radiotherapy with immune checkpoint inhibitor (ICI) treatment has emerged as an important therapeutic regimen. However, this combined treatment may increase the risk of pneumonitis. The aim of this study is to analyze the incidence and risk factors for pneumonitis in non-small cell lung cancer (NSCLC) patients receiving combined thoracic radiotherapy and ICI (RT + ICI) treatment in the real-world clinical setting, offering a reference and guidance for clinical physicians. Methods This study identified 447 patients with pathologically confirmed NSCLC at West China Hospital of Sichuan University from 2016 to 2021. Clinical characteristics, treatment regimens, immune-related adverse events (irAEs), and hematological data were collected and analyzed. Results Patients receiving combined RT + ICI treatment had a higher risk of developing pneumonitis than those receiving ICI treatment alone (26.9 vs. 6.7 %, p<0.001). The multivariate logistic analysis identified the following independent risk factors for pneumonitis in patients undergoing combined RT + ICI treatment: history of lung disease (p=0.032), first-line ICI treatment (p=0.001), anti-PD-L1 instead of anti-PD-1 treatment (p=0.035), and the development of immunotherapy-related thyroid dysfunction (p=0.019). The independent risk factors were incorporated into a nomogram to predict the incidence of pneumonitis. The area under the receiver operating characteristic curve is 0.727, suggesting an acceptable predictive efficacy. Conclusions Compared to ICI monotherapy, NSCLC patients receiving the combination of thoracic radiotherapy and ICI treatment are at higher risk of developing pneumonitis. The nomogram holds promise for facilitating the risk assessment and early identification of pneumonitis in NSCLC patients receiving combined RT + ICI treatment.

Efficacy and safety of tyrosine kinase inhibitors with thoracic radiotherapy for patients with oncogene-mutated non-small cell lung cancer: a meta-analysis.

Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients. The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT. This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively. In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients.

Effects of ultra-high dose rate radiotherapy with different fractions and dose rate on acute and chronic lung injury in mice

Ultra-high dose rate radiotherapy (FLASH radiation) can naturally render normal tissues around the tumor tissue resistant to radiotherapy. In contrast, the tumor tissue remains sensitive to radiation under the same conditions. However, the effects of different fractions and dose rates on FLASH radiation remain unclear. This study aimed to determine the optimal dose rate and fraction of FLASH radiation for thoracic radiotherapy. Female Balb/c mice aged 6–8 weeks were irradiated with different dose rates (100 Gy/s or 250 Gy/s) and fractions (1, 2, or 4). Survival was observed in mice receiving 30Gy, with lung tissue examined for acute radiation damage 48 h post-radiation. Late radiation pneumonia and survival rates were monitored in mice irradiated with 20 Gy. The median overall survival (OS) was not reached on the 95th day for mice irradiated with 250 Gy/s FLASH radiation, while it was 89.5 days for those irradiated with 100 Gy/s (P = 0.0436). Mice irradiated with 30 Gy/2 Fr and 250 Gy/s FLASH had shorter median OS than those with 30 Gy/1F (P = 0.0132). However, there was no significant difference in OS between mice irradiated with 30 Gy/2 F and 30 Gy/4 F. Survival curves for mice receiving 20 Gy showed no significant difference in toxicity between different dose rates and fractions. FLASH radiation at 250 Gy/s reduced the incidence of acute radiation pneumonitis in mice compared to 100 Gy/s. Different fractions of irradiation influenced survival in mice, but they were only observed in acute radiation reactions and not chronic radiation reactions. Among the tested fraction methods, fraction 2 had the worst impact on the survival of mice, while fractions 1 and 4 showed similar effects and improved survival compared to fraction 2.

Germline Human Leukocyte Antigen Status is Associated With Immunotherapy-Induced Pneumonitis and Treatment Response in Patients With Non–Small Cell Lung Cancer With High Programmed Death-Ligand 1 Expression

IntroductionThe germline human leukocyte antigen (HLA) status has been found to be associated with immunotherapy outcomes in patients with NSCLC, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. MethodsWe evaluated the HLA genotype of the germline and available tumor samples in 42 patients with programmed death-ligand 1 expression of 50% or higher undergoing pembrolizumab immunotherapy. The HLA allele expression was correlated with tumor response, disease survival, and the occurrence of pneumonitis. ResultsIt was observed that the germline HLA-C homozygosity and HLA-DRB1∗13 expression were related to a worse progression-free survival and treatment response. Importantly, all patients (7/7 patients) who developed pneumonitis in our cohort expressed the HLA-DPB1∗02 allele, and the incidence of pneumonitis was 31.8% (7/22 patients) in patients expressing this allele compared with 0% (0/20 patients) in those without this allele (p = 0.009). Investigation of the tumor samples from 15 patients revealed some degree of HLA loss in the HLA class I loci in 40% (6/15) of patients, and no significant difference in tumor mutation burden was found among patients with different treatment responses. ConclusionTaken together, this study evaluated the impact of HLA status in both germline and tumor samples in patients with NSCLC with high programmed death-ligand 1 expression, and the high incidence of immunotherapy-induced pneumonitis in patients expressing the HLA-DPB1∗02 allele may suggest a routine HLA typing and closer monitoring in this patient subset.

Comparison of efficacy of gefitinib and osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer in patients with poor performance status

BackgroundThere is a dearth of studies on the efficacy and safety of the tyrosine kinase inhibitors osimertinib (OSI) and gefitinib (GEF) in treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS). MethodsWe retrospectively reviewed and compared data of 113 patients with EGFR mutation-positive NSCLC with Eastern Cooperative Oncology Group PS 2–4 who were administered OSI 80 mg/day or GEF 250 mg/day from May 2016 to March 2022. ResultsThe GEF group (39 patients; median age: 74 years) included 20 patients with a PS of 2, 17 with a PS of 3, and 2 with a PS of 4. The OSI group (74 patients; median age: 76 years) included 48 patients with a PS of 2, 24 with a PS of 3, and 2 with a PS of 4. The overall response rates were 69% and 66% in the GEF and OSI groups, respectively. The disease control and PS improvement rates were 89% and 51% in both groups, respectively. The median progression-free survival in the GEF and OSI groups was 6.9 and 9.2 months, respectively (p = 0.15). The OSI group experienced better overall survival than the GEF group (median: 20.9 vs. 13.0 months, p = 0.0031). The incidence of pneumonitis was 10% and 11% in the GEF and OSI groups, respectively. One treatment-related death owing to pneumonitis occurred in the GEF group. ConclusionsOSI may be a useful treatment for untreated EGFR mutation-positive NSCLC with poor PS.

P2.05A.02 Incidence of Pneumonitis in Asian Patients with Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis

P2.05A.02 Incidence of Pneumonitis in Asian Patients with Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

3170: Impact of Tumor Margins on Radiation Pneumonitis Incidence in Advanced Stage NSCLC Radiotherapy

3170: Impact of Tumor Margins on Radiation Pneumonitis Incidence in Advanced Stage NSCLC Radiotherapy

Appropriate delay of primary tumour radiotherapy may lead to better long-term overall survival for non-small cell lung cancer treated with EGFR-TKIs

PurposeThe most appropriate time of primary tumor radiotherapy in non-small cell lung cancer(NSCLC) with EGFR-TKIs remains unclear. The aim of this study was to investigate the effect of the time factor of primary tumor radiotherapy on long-term overall survival(OS)and provide a theoretical basis for further clinical research.Patients and methodsIn total, 238 patients with EGFR-TKIs and OS ≥ 12 months were statistically analysed. Patients were grouped: the D group without primary tumor radiotherapy and the R group with it.The R group were divided into three groups according to the interval between the start of EGFR-TKIs and the start of primary tumor radiotherapy: R0 − 30(<30 days), R30 − PD(≥ 30 days and disease stable), and RPD(radiotherapy after disease progression). The Kaplan-Meier method and log-rank test were used for survival analyses. Exploratory landmark analyses were investigated. ResultsThe OS rates at 1, 2, 3, 5 years for the R group and D group were 96.8%, 62.9%, 38.3%, 17.1%, and 95.6%, 37.7%, 21.8%, 2.9%, respectively; the corresponding MST was 29 months(95% CI: 24.3–33.7) for the R group and 22 months(95% CI: 20.4–23.6) for the D group (χ2 = 13.480, p<0.001). Multivariate analysis revealed that primary tumor radiotherapy was independent predictors of prolonged OS.Among the four groups, The R30 − PD appeared to have the best OS (D, χ2 = 19.307, p<0.001;R0 − 30, χ2 = 11.687, p = 0.01; RPD, χ2 = 4.086, p = 0.043). Landmark analyses(22 months) showed the R30 − PD group had a significant long-term OS.The incidence of radiation pneumonitis ≥ grade 2 was17.3%(n = 19)and radiation esophagitis ≥ grade 2 was observed in 32 patients(29.1%).ConclusionsOur results showed that primary tumour radiotherapy may prolong long-term OS with acceptable toxicities. Appropriate delay(R30 − PD)of primary tumour radiotherapy may be the best choice.Premature radiotherapy(R0 − 30) and radiotherapy after disease progression (RPD)may not be reasonable for long-term OS.

A novel predictor for dosimetry data of lung and the radiation pneumonitis incidence prior to SBRT in lung cancer patients

Normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) in lung cancer patients with stereotactic body radiation therapy (SBRT), which based on dosimetric data from treatment planning, are limited to patients who have already received radiation therapy (RT). This study aims to identify a novel predictive factor for lung dose distribution and RP probability before devising actionable SBRT plans for lung cancer patients. A comprehensive correlation analysis was performed on the clinical and dose parameters of lung cancer patients who underwent SBRT. Linear regression models were utilized to analyze the dosimetric data of lungs. The performance of the regression models was evaluated using mean squared error (MSE) and the coefficient of determination (R2). Correlational analysis revealed that most clinical data exhibited weak correlations with dosimetric data. However, nearly all dosimetric variables showed "strong" or "very strong" correlations with each other, particularly concerning the mean dose of the ipsilateral lung (MI) and the other dosimetric parameters. Further study verified that the lung tumor ratio (LTR) was a significant predictor for MI, which could predict the incidence of RP. As a result, LTR can predict the probability of RP without the need to design an elaborate treatment plan. This study, as the first to offer a comprehensive correlation analysis of dose parameters, explored the specific relationships among them. Significantly, it identified LTR as a novel predictor for both dose parameters and the incidence of RP, without the need to design an elaborate treatment plan.

Preliminary Results of Developing Imaging Complexity Biomarkers for the Incidence of Severe Radiation Pneumonitis Following Radiotherapy in Non-Small Cell Lung Cancer Patients with Underlying Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) has the potential to cause fatal pulmonary toxicity after radiotherapy and can increase the morbidity and mortality of non-small-cell lung cancer (NSCLC) patients. In this context, we aimed to develop imaging complexity biomarkers to predict the incidence of severe pulmonary toxicity in patients with NSCLC who have underlying IPF and are treated with radiotherapy. Methods: We retrospectively reviewed the medical records of 19 patients with NSCLC who had underlying IPF and were treated with radiotherapy at the Korea University Guro Hospital between March 2018 and December 2022. To quantify the morphometric complexity of the lung parenchyma, box-counting fractal dimensions and lacunarity analyses were performed on pre-radiotherapy simulation chest computed tomography scans. Results: Of the 19 patients, the incidence of grade 3 or higher radiation pneumonitis was observed in 8 (42.1%). After adjusting for age, sex, smoking status, histology, and diffusing capacity of the lung for carbon monoxide, eight patients with a lower fractal dimension showed a significantly higher hazard ratio of 7.755 (1.168-51.51) for grade 3 or higher pneumonitis than those with a higher fractal dimension. Patients with lower lacunarity exhibited significantly lower hazards in all models, both with and without adjustments. The lower-than-median lacunarity group also showed significantly lower incidence curves for all models built in this study. Conclusions: We devised a technique for quantifying morphometric complexity in NSCLC patients with IPF on radiotherapy and discovered lacunarity as a potential imaging biomarker for grade 3 or higher pneumonitis.

Pneumonitis Incidence in Patients With Metastatic Non-small Cell Lung Cancer on Immunotherapy: A Systematic Review and Meta-Analysis.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often diagnosed at the advanced stage (metastatic). Treatment options for metastatic NSCLC include radiotherapy, chemotherapy, target drug therapy, and immunotherapy. Immunotherapy (utilization of checkpoint inhibitors) boosts the immune system to recognize and destroy cancer cells. However, it is often associated with immune-related complications such as pneumonitis. This review aims to determine the incidence of pneumonitis in metastatic NSCLC patients treated with different immunotherapy drugs. PubMed, Cochrane Library, and Embase databases were scoured for randomized controlled trials (RCTs) until October 2023. Published RCTs with similar research objectives were included, while non-English articles, reviews, case reports, ongoing trials, non-randomized studies, conference abstracts, and studies on small cell lung cancer (SCLC) were excluded. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess the risk of bias among the included studies. The statistical analyses were performed with the Comprehensive Meta-Analysis software. The subgroup analysis of the 16 included RCTs showed that metastatic NSCLC patients treated with nivolumab and pembrolizumab had a higher incidence of any grade pneumonitis than those treated withatezolizumab (4.5% and 5.1% vs. 1.6%, respectively). Similarly, the incidence of grade ≥3 pneumonitis was higher among patients receiving nivolumab (1.3%) and pembrolizumab (2.4%) than those receiving atezolizumab (0.7%). Furthermore, the subgroup analysis showed that patients with naive-treated NSCLC on immunotherapy had a higher incidence of any grade pneumonitis than those with previously treated NSCLC (6.5% vs. 3.9%). Treatment-naive patients recorded higher grade ≥3 pneumonitis incidences than those previously treated (3.1% vs. 1.3%). Programmed death 1 (PD-1) inhibitors (i.e., pembrolizumab and nivolumab) have higher incidences of pneumonitis than programmed death-ligand 1 inhibitors (atezolizumab).

Treatment Outcomes of Stereotactic Body Radiotherapy for Early-stage Non-small Cell Lung Cancer and Lung Metastasis

Background and rationale: Stereotactic body radiotherapy (SBRT) is a highly precise localized high-dose per fraction radiation treatment used mainly in lung cancer. Despite SBRT's increasing use, no clear predictive factors of outcome exist. Objectives: To report local control rates, patterns of failure, and incidence of treatment-related toxicity, and to determine factors predicting SBRT outcomes for primary and secondary lung tumors at Ramathibodi Hospital using competing risk analysis. Materials and methods: This retrospective study included all patients diagnosed with primary early non-small cell lung cancer (NSCLC) and lung metastasis in our radiosurgery and radiotherapy database registry between January 2009 and September 2018. Results: Fifty-nine patients (98 lung tumors) were studied; primary NSCLC and lung metastasis were 15.3% and 84.7%, respectively. Median follow-up was 16.8 months. The overall 1-year local control rate was 90.8%. The most common pattern of failure was distant failure (46.9%). The incidence of radiation pneumonitis (RP) grade ≥2 was 9.2%, and one of four patients with an ultra-central tumor developed grade 5 pulmonary toxicity. The predictive factor for local failure was the mean biological equivalent dose (BED) of the planning target volume (PTV), and for RP grade ≥2, the tumor's maximal diameter. BED PTV mean &lt;100 Gy had higher local failure than BED PTV mean ≥100 Gy (adjusted subdistribution hazard ratio 8.26; 95% confidence interval (CI) 1.76–38.68, p=0.007). Patients with tumors with maximal diameters ≥5 cm compared with those with maximal diameters &lt;5 cm had more RP grade ≥2 (adjusted subdistribution hazard ratio 5.34; 95% CI 1.52–18.69, p=0.009). The overall 1-year survival rate was 73.5%. Conclusions: Local control of lung tumors using SBRT was high with acceptable toxicity. BED PTV mean was a local control predictor. Large tumors correlated with symptomatic RP grade ≥2. SBRT should be used judiciously for ultra-central lung tumors.